Ravingerova T, Stetka R, Volkovova K, Pancza D, Dzurba A, Ziegelhöffer A, Styk J
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Mol Cell Biochem. 2000 Jul;210(1-2):143-51. doi: 10.1023/a:1007129708262.
Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i.v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectively suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additional protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. Preconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention did not cause any further reduction in the level of lactate. In conclusion, diabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolytic metabolites during ischemia can account for the enhanced resistance of diabetic hearts to ischemia as well as for the lack of further protection by preconditioning.
糖尿病心脏对缺血的敏感性可能增强或降低。长时间缺血的有害影响可通过预处理减轻，然而，关于其在病变心肌中的作用相对知之甚少。本研究旨在测试糖尿病心脏对缺血性心律失常的易感性以及预处理的效果。用链脲佐菌素（45mg/kg，静脉注射）使大鼠患糖尿病。1周后，将离体Langendorff灌注心脏在无预处理或经5分钟缺血和10分钟再灌注的一个周期诱导的预处理后，进行30分钟的左冠状动脉前降支闭塞。在缺血前后对预处理和未预处理的心脏中的糖原和乳酸含量进行评估。糖尿病心脏对缺血性心律失常更具抵抗力：与非糖尿病对照组相比，室性心动过速（VT）的发生率降至42%，仅17%的心脏出现短暂室颤（VF）（非糖尿病对照组VT为100%，VF为70%，包括持续性VF为36%；p<0.05）。预处理有效抑制了正常心脏中心律失常的发生率和严重程度（VT为33%，VF为0%）。然而，这种干预在糖尿病心脏中并未提供任何额外的保护。尽管糖尿病心肌中的糖原含量较高且在缺血期间糖原分解较多，但这些心脏中的乳酸生成明显低于对照组。预处理使正常心脏中的乳酸积累大幅减少，而在糖尿病心脏中，这种干预并未使乳酸水平进一步降低。总之，糖尿病大鼠心脏对缺血性损伤的易感性较低，且对预处理无额外反应。缺血期间糖酵解代谢产物生成减少可解释糖尿病心脏对缺血的抵抗力增强以及预处理缺乏进一步保护作用的原因。
